rs1278377

chr10-126180909-G-Achr10-126180909-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001288973.2(ADAM12):c.261-25604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,112 control chromosomes in the GnomAD database, including 34,297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (34297 hom., cov: 32)
• Consequence: ADAM12 NM_001288973.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM12	NM_001288973.2	c.261-25604C>T		intron_variant		ENST00000448723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2	c.261-25604C>T		intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368676.8	c.261-25604C>T		intron_variant		1		A2
ADAM12	ENST00000368679.8	c.261-25604C>T		intron_variant		1		P2

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97918 AN: 151994 Hom.: 34232 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.629

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.645 AC: 98041 AN: 152112 Hom.: 34297 Cov.: 32 AF XY: 0.645 AC XY: 47979 AN XY: 74340

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.631

Alfa AF: 0.523 Hom.: 26679

Bravo AF: 0.677

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.0
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1278377; hg19: chr10-127869478;